Studies in our laboratory have demonstrated that bias (chloromethyl)ether (BCME) and chloromethyl methyl ether, both alkylating agents, are potent respiratory tract carcinogens. It has further been observed that low levels of BCME may be formed by the gas phase reaction of formaldehyde and hydrogen chloride. Our limited preliminary work suggests that the combined vapors at low levels of 10 ppm hydrogen chloride and 14.5 ppm formaldehyde caused carcinogenic effects in rats. Since both of these chemicals are extensively used, often in close proximity, this represents a potential hazard of great magnitude. The proposed study is designed to 1) determine the carcinogenic effects of these exposures and 2) determine possible carcinogenic effects of these chemicals when given separately. To date, animals have received 294 exposures over 453 days. The rate of mortality did not change significantly up to 32 weeks. After 32 weeks, there was an increase in groups receiving the combined exposures compared to those receiving formaldehyde alone. Nasal tumors were induced in both groups of combined exposures and in the formaldehyde groups. The times to first tumor in all 3 groups ranged from 403 to 443 days. All the tumors were squamous cell carcinomas of the nasal cavity. The study is still in progress.